Numerous pharmacologically active ingredients are unstable in the presence of water. Thus, where such ingredients are topically applied to the skin, delivery will typically require use of a hydrophobic vehicle. Unfortunately, hydrophobic vehicles generally absorb poorly into the skin and often lack a desirable look and feel.
For example, while some sunscreen formulations will remain almost completely on the surface of the skin to provide protection against UV irradiation, they will often give a greasy look or feel to a user. In another example, various lip stick or lip balm formulations will be partly absorbed to provide both, a soft feel to the lip as well as the desired coloring on the surface of the lip. However, most of these formulations will only poorly adhere to the lip and are typically formulated to provide a residual lipophilic coat on the lip. Where a pharmaceutically active agent is to be delivered into the skin from a hydrophobic vehicle, skin penetration enhancers may be included into such formulations to enhance delivery.
Exemplary penetration enhancers, compositions including same, and methods of use are described in WO 93/23019, WO 93/23025, EP 569338, EP 581587, WO 96/03131, or WO 97/06788. Most of the known penetration enhancers provide a significant improvement in delivery of a specific pharmaceutically active molecule through skin. However, the effect of such enhancers on the absorption of the entire preparation is often less than desirable in hydrophobic preparations. Therefore, even if the penetration enhancer increases flux of a pharmaceutically active molecule through the skin, the vehicle typically remains on the skin in relatively high quantities.
To circumvent at least some of the problems associated with remaining vehicle on the skin, various approaches shave been taken. For example, uptake of a hydrophobic vehicle may be forced using occlusive topical administration in which the vehicle is continuously presented to the skin (e.g., under of a film forming polymer or preformed barrier material). Occlusion generally tends to increase uptake of hydrophobic compositions into the skin, however, has several disadvantages. Among other things, occlusive preparations often need to remain attached to the skin over a prolonged period of time, which tends to present problems associated with: low tolerance to such compositions. Moreover, occlusive preparations are generally limited to use on non-facial skin and are only rarely (if ever) used on lips.
In another approach, an additive may be provided to the topical formulation that increases uptake of the formulation (i.e., vehicle and the pharmaceutically active agent) as described by Hrabalek et al. in U.S. Pat. No. 6,187,938. Here, certain omega amino acid derivatives are used to enhance penetration of a hydrophobic vehicle through skin. Similarly, as described in U.S. Pat. No. 4,892,890 to Damani, propylene glycol is used to increase uptake of the hydrophobic analgesic formulation. While such formulations have generally increased vehicle uptake, various difficulties still remain. Among other things, stability of at least some of the omega amino acid derivatives may be less than desirable. Furthermore, not all of the omega amino acids may be tolerated well, especially over a prolonged period of administration. Similarly, while propylene glycol increases vehicle absorption where the vehicle comprises significant quantities of waxes, propylene glycol (and other polyhydroxy compounds) will not increase absorption of other known hydrophobic vehicles equally well.
Thus, although various compositions and methods are known in the art to provide hydrophobic compositions to the skin, all or almost all of them suffer from one or more disadvantage. Therefore, there is still a need to provide improved compositions and methods for delivery of hydrophobic compositions to the skin.